JP5953358B2 - Ophthalmic composition for silicone hydrogel contact lens - Google Patents

Description

  The present invention relates to an ophthalmic composition for silicone hydrogel contact lenses. More specifically, an ophthalmology for a silicone hydrogel contact lens that can suppress lipid adsorption to a nonionic silicone hydrogel contact lens or can suppress the accumulation of pollen protein on an ionic silicone hydrogel contact lens. Relates to the composition. The present invention also relates to a method for suppressing lipid adsorption to a nonionic silicone hydrogel contact lens. The present invention also relates to a method for suppressing the accumulation of pollen proteins in ionic silicone hydrogel contact lenses.

In recent years, the number of wearers of contact lenses (hereinafter sometimes referred to as CL) is increasing, and among them, the number of wearers of soft contact lenses (hereinafter also sometimes referred to as SCL) is increasing. In general, it has been pointed out that when a soft contact lens is worn, the amount of oxygen supplied from the atmosphere decreases, which may result in suppression of corneal epithelial cell division and thickening of the cornea. Therefore, development of soft contact lenses having higher oxygen permeability has been advanced.

  Under such circumstances, silicone hydrogel contact lenses (hereinafter sometimes referred to as SHCL) have been developed in recent years as soft contact lenses having high oxygen permeability. Silicone hydrogel contact lenses achieve oxygen permeability several times that of conventional hydrogel contact lenses by blending silicone with hydrogel. Therefore, it is highly expected that the oxygen supply shortage, which is a weak point of the soft contact lens, can be improved and the adverse effects on the cornea due to the oxygen shortage can be greatly suppressed.

On the other hand, it has been pointed out that silicone hydrogel contact lenses are more likely to be contaminated with lipids derived from tear film, cosmetics and the like as compared with conventional hydrogel contact lenses (Non-patent Document 1). Such lipid contamination induces cloudiness of the lens, causing discomfort to the wearer and harming the quality of life (QOL). Further, such contamination of the contact lens may adversely affect the vision correction power that the lens should originally have. Furthermore, in recent years, it has also been pointed out that such lipid contamination of contact lenses affects the occurrence of corneal epithelial disorder called corneal staining.

  Therefore, it is indispensable to design an ophthalmic composition used for a contact lens with sufficient consideration of safety and other effects depending on the type of contact lens. In particular, since soft contact lenses are made of different materials, it is important that the ophthalmic composition used for the soft contact lens is designed according to the characteristics of the target soft contact lens.

  Moreover, hay fever is an allergic symptom caused by pollen protein contained in pollen becoming an antigen and contacting mucous membranes. In recent years, the number of patients with hay fever is increasing, which is becoming a major social problem. In the field of ophthalmology, there is a strong demand for the development of ophthalmic compositions useful for preventing hay fever and suppressing deterioration.

On the other hand, polyhexanide and its salts have been known to have an antiseptic action and are used in ophthalmic compositions (see Patent Document 1). In addition, chlorpheniramine, cromoglycic acid, pranoprofen, glycyrrhizic acid, neostigmine and their salts are also known to have useful effects such as antiallergic action, anti-inflammatory action, and improvement of eye focus control function. It is used for things. However, the effect of these components on the soiling of silicone hydrogel contact lenses has not been clarified. Moreover, the present situation is that it is not even possible to infer the influence of a combination of these specific components on the silicone hydrogel contact lens.

JP 2001-501605 A

Hiroshi Shiotani, New Ophthalmology Vol.25, No.7, 907-912, 2008

As a result of various studies on the lipid adsorption characteristics of various soft contact lenses, the present inventors have found that nonionic silicone hydrogel contact lenses (hereinafter sometimes referred to as nonionic SHCL) are soft contact lenses. Among them, it was confirmed that lipids were remarkably easily adsorbed. Such significant lipid stains can cause clouding of the lens, harming the wearer's QOL (Quality of Life), and may also adversely affect the vision correction ability of the lens.
Furthermore, such lipid stains may induce corneal epithelial disorders such as corneal staining. Therefore, by suppressing lipid adsorption to nonionic SHCL, it prevents the cloudiness of the lens and improves the feeling of wearing, maintains the original vision correction power of the lens, and prevents the occurrence of corneal epithelial disorder. Therefore, there is a demand for the development of a means that makes it possible to use SHCL comfortably and safely.

  Furthermore, the present inventors have conducted various studies on the adsorption properties of pollen proteins to various soft contact lenses. As a result, pollen is not used for ionic silicone hydrogel contact lenses (hereinafter also referred to as ionic SHCL). We obtained a completely new finding that the protein is remarkably easy to adsorb. In general, proteins are thought to be difficult to adsorb to SHCL, and this finding is completely unexpected. And generally, when wearing contact lenses, the eyes are likely to dry, and as a result, the cleaning action by tears is reduced, and foreign substances such as pollen are likely to stay in the eyes, which increases the risk of developing hay fever. It is considered. Moreover, if a large amount of pollen protein is adsorbed and accumulated on the contact lens, the risk of developing hay fever is significantly increased, which may contribute to the induction or seriousness of allergic symptoms. Furthermore, if the pollen protein adsorbed on the contact lens is insufficiently removed, the wearing feeling of the contact lens is impaired, causing discomfort and fogging of the contact lens, and shortening the use period. Therefore, the development of means that can suppress the accumulation of pollen protein in ionic SHCL is required.

  Then, one of the objectives of this invention is providing the ophthalmic composition for SHCL which can suppress the lipid adsorption | suction to nonionic SHCL. Another object of the present invention is to provide an ophthalmic composition for SHCL that can suppress the accumulation of pollen protein in ionic SHCL or that can wash pollen protein adsorbed on ionic SHCL. It is to be.

As a result of intensive studies to solve the above problems, the present inventors have found that (A) at least one selected from the group consisting of polyhexanide and a salt thereof, and (B) chlorpheniramine, cromoglycic acid, pranopro It has been found that by using in combination with at least one selected from the group consisting of phen, glycyrrhizic acid, neostigmine, and salts thereof, the lipid adsorption to nonionic SHCL can be remarkably suppressed. Further, the present inventors have found that the combined use of the above components makes it possible to suppress the accumulation of pollen protein in ionic SHCL and can effectively wash the pollen protein adsorbed on ionic SHCL. The present invention has been completed by making further improvements based on such findings.

［式(1)中、R₁及びR₂は、同一又は異なって、下記一般式(2)に示される基又はアミノ基であり、ｎは１〜５００の整数を示す。］

項1-3.式(1)中、R₁はアミノ基であり、且つR₂は一般式(2)に示される基である、項1-2に
記載のシリコーンハイドロゲルコンタクトレンズ用眼科組成物。
項1-4．(A)成分として、ポリヘキサニドの塩酸塩を含む、項1-1〜1-3のいずれかに記載のシリコーンハイドロゲルコンタクトレンズ用眼科組成物。
項1-5．(A)成分を総量で0.000005〜0.002w/v％含有する、項1-1〜1-4のいずれかに記載のシリコーンハイドロゲルコンタクトレンズ用眼科組成物。
項1-6．(B)成分として、マレイン酸クロルフェニラミン、クロモグリク酸ナトリウム、プラノプロフェン、グリチルリチン酸二カリウム及びメチル硫酸ネオスチグミンからなる群より選択される少なくとも１種を含む、項1-1〜1-5のいずれかに記載のシリコーンハイドロゲルコンタクトレンズ用眼科組成物。
項1-7．(B)成分を総量で0.0005〜3.5w/v％含有する、項1-1〜1-6のいずれかに記載のシリコーンハイドロゲルコンタクトレンズ用眼科組成物。
項1-8． 更に、緩衝剤を含有する、項1-1〜1-7のいずれかに記載のシリコーンハイドロ
ゲルコンタクトレンズ用眼科組成物。
項1-9． 緩衝剤としてホウ酸緩衝剤を含む、項1-8に記載のシリコーンハイドロゲルコンタクトレンズ用眼科組成物。
項1-10． 緩衝剤を総量で0.01〜10w/v％含有する、項1-8又は1-9に記載のシリコーンハ
イドロゲルコンタクトレンズ用眼科組成物。
項1-11． 更に、等張化剤を含有する、項1-1〜1-10のいずれかに記載のシリコーンハイ
ドロゲルコンタクトレンズ用眼科組成物。
項1-12． 等張化剤として、塩化ナトリウム、塩化カリウム、塩化カルシウム、塩化マグネシウム、グリセリン、及びプロピレングリコールからなる群より選択される少なくとも１種を含む、項1-11に記載のシリコーンハイドロゲルコンタクトレンズ用眼科組成物。
項1-13． 等張化剤を総量で0.01〜10w/v％含有する、項1-11又は1-12に記載のシリコー
ンハイドロゲルコンタクトレンズ用眼科組成物。
項1-14． 更に、界面活性剤を含有する、項1-1〜1-13のいずれかに記載のシリコーンハ
イドロゲルコンタクトレンズ用眼科組成物。
項1-15． 界面活性剤として非イオン性界面活性剤を含む、項1-14に記載のシリコーンハイドロゲルコンタクトレンズ用眼科組成物。
項1-16． 界面活性剤を総量で0.01〜10w/v％含有する、項1-14又は1-15に記載のシリコ
ーンハイドロゲルコンタクトレンズ用眼科組成物。
項1-17． 点眼剤である、項1-1〜1-16のいずれかに記載のシリコーンハイドロゲルコン
タクトレンズ用眼科組成物。
項1-18． 非イオン性シリコーンハイドロゲルコンタクトレンズ用である、項1-1〜1-17
のいずれかに記載のシリコーンハイドロゲルコンタクトレンズ用眼科組成物。
項1-19． イオン性シリコーンハイドロゲルコンタクトレンズ用である、項1-1〜1-17の
いずれかに記載のシリコーンハイドロゲルコンタクトレンズ用眼科組成物。 That is, the present invention provides the following ophthalmic compositions for SHCL.
Item 1-1. (A) at least one selected from the group consisting of polyhexanide and salts thereof, and (B) at least selected from the group consisting of chlorpheniramine, cromoglycic acid, pranoprofen, glycyrrhizic acid, neostigmine and salts thereof. An ophthalmic composition for a silicone hydrogel contact lens, comprising:
Item 1-2. The silicone hydrogel contact lens according to Item 1-1, comprising as component (A) at least one selected from the group consisting of a compound represented by the following general formula (1) and a salt thereof: Ophthalmic composition.

[In formula (1), R ₁ and R ₂ are the same or different, group or represented by the following general formula (2) is an amino group, n represents an integer of 1 to 500. ]

Item 1-3. The ophthalmic composition for a silicone hydrogel contact lens according to Item 1-2, wherein, in Formula (1), R ₁ is an amino group, and R ₂ is a group represented by Formula (2) object.
Item 1-4. Item 4. The ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 1-1 to 1-3, which contains polyhexanide hydrochloride as the component (A).
Item 1-5. Item 5. The ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 1-1 to 1-4, wherein the total amount of component (A) is 0.000005 to 0.002 w / v%.
Item 1-6. Item (B) includes at least one selected from the group consisting of chlorpheniramine maleate, sodium cromoglycate, pranoprofen, dipotassium glycyrrhizinate and neostigmine methyl sulfate, as component (1-1) The ophthalmic composition for silicone hydrogel contact lenses according to any one of the above.
Item 1-7. Item 5. The ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 1-1 to 1-6, wherein the component (B) is contained in a total amount of 0.0005 to 3.5 w / v%.
Item 1-8. The ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 1-1 to 1-7, further comprising a buffer.
Item 1-9. Item 9. The ophthalmic composition for silicone hydrogel contact lenses according to Item 1-8, which contains a borate buffer as a buffer.
Item 1-10. Item 10. The ophthalmic composition for silicone hydrogel contact lens according to Item 1-8 or 1-9, comprising a buffering agent in a total amount of 0.01 to 10 w / v%.
Item 1-11. Item 10. The ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 1-1 to 1-10, further comprising an isotonic agent.
Item 1-12. The ophthalmology for silicone hydrogel contact lenses according to Item 1-11, which contains at least one selected from the group consisting of sodium chloride, potassium chloride, calcium chloride, magnesium chloride, glycerin, and propylene glycol as an isotonic agent. Composition.
Item 1-13. Item 13. The ophthalmic composition for silicone hydrogel contact lenses according to Item 1-11 or 1-12, which contains an isotonic agent in a total amount of 0.01 to 10 w / v%.
Item 1-14. Item 14. The ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 1-1 to 1-13, further comprising a surfactant.
Item 1-15. Item 15. The ophthalmic composition for silicone hydrogel contact lenses according to Item 1-14, which contains a nonionic surfactant as a surfactant.
Item 1-16. Item 15. The ophthalmic composition for silicone hydrogel contact lenses according to Item 1-14 or 1-15, wherein the surfactant is contained in a total amount of 0.01 to 10 w / v%.
Item 1-17. The ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 1-1 to 1-16, which is an eye drop.
Item 1-18. Item 1-1 to 1-17 for nonionic silicone hydrogel contact lenses
The ophthalmic composition for silicone hydrogel contact lenses according to any of the above.
Item 1-19. The ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 1-1 to 1-17, which is for ionic silicone hydrogel contact lenses.

Moreover, this invention provides the method of suppressing adsorption | suction of the lipid to the nonionic silicone hydrogel contact lens hung up below.
Item 2. (A) at least one selected from the group consisting of polyhexanide and salts thereof, and (B)
An ophthalmic composition for a silicone hydrogel contact lens containing at least one selected from the group consisting of chlorpheniramine, cromoglycic acid, pranoprofen, glycyrrhizic acid, neostigmine and salts thereof, and a nonionic silicone hydrogel A method for suppressing adsorption of lipids to a nonionic silicone hydrogel contact lens, which comprises contacting the contact lens.

The present invention also provides a method for imparting lipid adsorption inhibiting action to nonionic SHCL to the following ophthalmic compositions for SHCL.
Item 3. In the ophthalmic composition for silicone hydrogel contact lens, (A) polyhexanide,
And (B) at least one selected from the group consisting of chlorpheniramine, cromoglycic acid, pranoprofen, glycyrrhizic acid, neostigmine, and salts thereof. A method of imparting an action of suppressing lipid adsorption to a nonionic silicone hydrogel contact lens to an ophthalmic composition for a silicone hydrogel contact lens.

Moreover, this invention provides the method of suppressing accumulation | storage of pollen protein to ionic SHCL hung up below.
Item 4. (A) at least one selected from the group consisting of polyhexanide and salts thereof, and (B)
An ophthalmic composition for a silicone hydrogel contact lens, comprising at least one selected from the group consisting of chlorpheniramine, cromoglycic acid, pranoprofen, glycyrrhizic acid, neostigmine and a salt thereof, an ionic silicone hydrogel contact A method for suppressing the accumulation of pollen protein in an ionic silicone hydrogel contact lens, comprising contacting the lens.

Moreover, this invention provides the method of providing the accumulation | storage suppression effect | action of the pollen protein to ionic SHCL to the ophthalmic composition for SHCL shown below.
Item 5. In an ophthalmic composition for silicone hydrogel contact lenses, (A) at least one selected from the group consisting of polyhexanide and salts thereof, and (B) chlorpheniramine, cromoglycic acid, pranoprofen, glycyrrhizic acid, neostigmine and A method for imparting to the ophthalmic composition an action of suppressing the accumulation of pollen proteins in an ionic silicone hydrogel contact lens, comprising blending at least one selected from the group consisting of these salts.

  The ophthalmic composition for SHCL of the present invention can remarkably suppress lipid adsorption to nonionic SHCL. Therefore, according to the ophthalmic composition for SHCL of the present invention, non-ionic SHCL lipid fouling is prevented, non-ionic SHCL cloudiness is prevented, and the non-ionic SHCL use feeling is kept good. Nonionic SHCL's original vision correction power can be maintained, and corneal epithelial disorders such as corneal staining caused by adsorption of lipid stains on SHCL can be effectively prevented, and comfortably and safely nonionic It becomes possible to use SHCL.

  Furthermore, according to the ophthalmic composition for SHCL of the present invention, even when pollen protein comes into contact with ionic SHCL during wearing of ionic SHCL, it promotes removal of pollen protein from ionic SHCL and prevents reattachment. By doing so, accumulation of pollen protein in ionic SHCL can be suppressed. Therefore, the risk of developing allergic symptoms can be reduced for users of hay fever or pollinosis reserves. Furthermore, according to the ophthalmic composition for SHCL of the present invention, the ionic SHCL can be kept clean during or before wearing the ionic SHCL, and the feeling of use of the ionic SHCL can also be kept good.

  In this way, the ophthalmic composition for SHCL of the present invention can solve the problems concerned at the time of wearing nonionic and ionic SHCL at a time, so that high safety and comfort are ensured in the use of SHCL. Can do.

In the reference test example 1, it is a figure which shows the result of having evaluated the adsorption | suction characteristic of the lipid in various soft contact lenses. In Experiment 1, it is a figure which shows the result of having evaluated the influence which acts on adsorption | suction of the lipid to SHCL about a test liquid (Examples 1-1 to 1-5 and Comparative Examples 1-1 to 1-6). In Test Example 1, it is a figure which shows the result of having evaluated the influence which acts on adsorption | suction of the lipid to SHCL about a test liquid (Examples 1-6 to 1-11 and Comparative Examples 1-7 to 1-12). In Test Example 1, it is a figure which shows the result of having evaluated the influence which it has on the adsorption | suction of the lipid to SHCL about the test liquid (Examples 1-12 to 1-16 and Comparative Examples 1-13 to 1-18). In the reference test example 2, it is a figure which shows the result of having evaluated the adsorptivity of the pollen protein to various soft contact lenses. In Test Example 2, it is a figure which shows the result of having evaluated the effect which the test liquid (Example 2-1 to 2-2, Comparative Example 2-1 to 2-3) removes the pollen protein adsorbed to ionic SHCL. .

1. Ophthalmic Composition for SHCL The ophthalmic composition for SHCL of the present invention contains at least one selected from the group consisting of polyhexanide and a salt thereof (hereinafter also referred to as (A) component or PHMB).

  The polyhexanide used in the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. The compound shown in (1) is exemplified.

In the general formula (1), R ₁ and R ₂ are the same or different and represent a group or an amino group represented by the following general formula (2). Preferably, R ₁ is an amino group, and R ₂ is a group or an amino group represented by the general formula (2), more preferably R ₁ is an amino group, and R ₂ is represented by the general formula (2). Group.

Moreover, in general formula (1), n shows the integer of 1-500. Preferably, it represents an integer of 2 to 200, more preferably an integer of 4 to 100, and particularly preferably an integer of 8 to 20.

  The salt of polyhexanide is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Specific examples of polyhexanide salts include inorganic acid salts such as hydrochloric acid, hydrogen bromide, sulfuric acid, and boric acid; and organic acid salts such as acetic acid, gluconic acid, maleic acid, ascorbic acid, stearic acid, tartaric acid, and citric acid. Illustrated. Among these polyhexanide salts, inorganic acid salts are preferable, and hydrochlorides are more preferable. These polyhexanide salts may be used alone or in any combination of two or more.

In the ophthalmic composition for SHCL of the present invention, as the component (A), one of polyhexanide and a salt thereof may be used alone, or two or more of them may be used in any combination. May be. Among the components (A), from the viewpoint of further enhancing the lipid adsorption inhibitory action on nonionic SHCL, or further enhancing the accumulation inhibitory action of pollen protein on ionic SHCL, preferably polyhexanide or its inorganic acid salt, Preferred is polyhexanide or its hydrochloride, and particularly preferred is polyhexanide hydrochloride.

In the ophthalmic composition for SHCL of the present invention, the blending ratio of the component (A) is appropriately set according to the type of the component (A), the type of the component (B) to be used together, the formulation form of the ophthalmic composition for SHCL, etc. However, as an example, the total amount of component (A) is 0.000005 to 0.002 w / v%, preferably 0.00001 to 0.001 w / v%, more preferably 0.00005 to 0.0003 w based on the total amount of the ophthalmic composition for SHCL. / v% is exemplified.

The blending ratio of the component (A) is suitable from the viewpoint of further enhancing the lipid adsorption inhibiting action on nonionic SHCL and further enhancing the action of inhibiting the accumulation of pollen proteins in ionic SHCL.

In addition to the component (A), the ophthalmic composition for SHCL of the present invention is at least one selected from the group consisting of chlorpheniramine, cromoglycic acid, pranoprofen, glycyrrhizic acid, neostigmine, and salts thereof (hereinafter referred to as “the component (A)”) And (B) component). By using the components (A) and (B) together in this way, it becomes possible to effectively suppress the adsorption of lipids to nonionic SHCL, and also effectively suppress the accumulation of pollen proteins in ionic SHCL. It becomes possible to make it.

  Among the components (B), cromoglycic acid is 5,5 ′-[(2-hydroxy-1,3-propanediyl) bis (oxy)] bis [4-oxo-4H-1-benzopyran-2- It is a known compound also referred to as “carboxylic acid”, and may be synthesized by a known method or may be obtained as a commercial product.

The salt of cromoglycic acid is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable, but for example, an alkali metal such as sodium salt and potassium salt and the like And salts with alkaline earth metals such as calcium salts and magnesium salts. Among these salts, an alkali metal salt is preferable, and a sodium salt is more preferable. These cromoglycic acid salts may be used alone or in any combination of two or more.

  Moreover, cromoglycic acid and its salt can be used also in the form of a hydrate.

  Among the cromoglycic acid and salts thereof, from the viewpoint of further enhancing the lipid adsorption inhibitory action on nonionic SHCL, or further enhancing the action of inhibiting the accumulation of pollen proteins in ionic SHCL, preferably a salt of cromoglycic acid, more preferably Is an alkali metal salt of cromoglycic acid, particularly preferably sodium cromoglycate.

Among the components (B), chlorpheniramine is 3- (4-chlorophenyl) -N, N-dimethyl-3-
It is a known compound, also called pyridin-2-yl-propan-1-amine, which may be synthesized by a known method or obtained as a commercial product.

  The salt of chlorpheniramine is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. For example, organic acid salts such as maleate and fumarate Inorganic salts such as hydrochloride and sulfate; various salts such as metal salts. Among these salts, an organic acid salt is preferable, and a maleic acid salt (chlorpheniramine maleate) is more preferable. These chlorpheniramine salts may be used alone or in any combination of two or more.

  Further, chlorpheniramine and a salt thereof may be in the form of a hydrate, and may be any of d-form, l-form, and dl-form.

  Among chlorpheniramine and salts thereof, from the viewpoint of further enhancing the lipid adsorption inhibitory action on nonionic SHCL, or further enhancing the accumulation inhibitory action of pollen protein on ionic SHCL, preferably a salt of chlorpheniramine, More preferred is an organic acid salt of maleic acid, and particularly preferred is chlorpheniramine maleate.

  In addition, of the component (B), pranoprofen is a known compound also called α-methyl-5H- [1] benzopyrano [2,3-b] pyridine-7-acetic acid. It may be synthesized or obtained as a commercial product.

  The salt of pranoprofen is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable, but for example, a salt with an alkali metal such as sodium salt or potassium salt. Salt with alkaline earth metal such as calcium salt and magnesium salt; salt with metal such as aluminum salt; methylamine salt, triethylamine salt, diethylamine salt, triethanolamine salt, morpholine salt, piperazine salt, pyrrolidine salt, tripyridine And salts with organic bases such as salts and picoline salts. These pranoprofen salts may be used alone or in any combination of two or more.

  Planoprofen and its salts can also be used in the form of hydrates.

  Of the pranoprofen and its salts, pranoprofen is preferred from the viewpoint of further enhancing the lipid adsorption inhibiting action on nonionic SHCL or further enhancing the accumulation inhibiting action of pollen protein on ionic SHCL. .

Glycyrrhizic acid is 20β-carboxy-11-oxo-30-noroleana-12-en-3β-yl
= (β-D-glucopyranosyluronic acid)-(1 → 2) -α-D-glucopyranoside uronic acid is a known compound, which is also a commercially available product that may be synthesized or extracted by a known method Can also be obtained as

  The salt of glycyrrhizic acid is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. For example, alkali metal such as sodium salt and potassium salt And ammonium salts and the like. More specifically, examples include salts with alkali metals such as disodium glycyrrhizinate, trisodium glycyrrhizinate, dipotassium glycyrrhizinate, and tripotassium glycyrrhizinate; ammonium salts such as monoammonium glycyrrhizinate. Among these, Preferably the alkali metal salt of glycyrrhizic acid, More preferably, dipotassium glycyrrhizinate is mentioned. These glycyrrhizic acid salts may be used alone or in any combination of two or more.

  Among glycyrrhizic acid and salts thereof, from the viewpoint of further enhancing the lipid adsorption inhibitory action on nonionic SHCL or further enhancing the inhibitory action on pollen protein accumulation in ionic SHCL, preferably a salt of glycyrrhizic acid, more preferably Is an alkali metal salt of glycyrrhizic acid, particularly preferably dipotassium glycyrrhizinate.

Among the components (B), neostigmine is a known compound also called N-(-3-dimethylcarbamoyloxyphenyl) -N, N, N-trimethylammonium, which can be synthesized by a known method. It can also be obtained as a commercial product.

  The salt of neostigmine is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. For example, methylsulphate (neostigmine methylsulfate), bromide salt (bromide) Neostigmine) and the like are exemplified. Among the salts of neostigmine, methyl sulfate is preferable. These neostigmine salts may be used alone or in any combination of two or more.

  Among neostigmine and salts thereof, from the viewpoint of further enhancing the lipid adsorption inhibitory action on nonionic SHCL or further enhancing the action of inhibiting pollen protein accumulation in ionic SHCL, preferably neostigmine salt, more preferably methyl. An example is neostigmine sulfate.

In the ophthalmic composition for SHCL of the present invention, the component (B) may be used alone from among chlorpheniramine, cromoglycic acid, pranoprofen, glycyrrhizic acid, neostigmine and salts thereof. Two or more kinds may be used in any combination. As a suitable example of the component (B) used in the present invention, chlorpheniramine maleate,
Examples include sodium cromoglycate, pranoprofen, dipotassium glycyrrhizinate and neostigmine methylsulfate.

Among the components (B) used in the present invention, from the viewpoint of further enhancing the lipid adsorption inhibitory action on nonionic SHCL, preferably chlorpheniramine, cromoglycic acid, pranoprofen, glycyrrhizic acid, and these Salt; more preferably, pranoprofen is exemplified.

In addition, from the viewpoint of further enhancing the action of suppressing the accumulation of pollen protein on ionic SHCL, the component (B) is preferably glycyrrhizic acid, neostigmine and salts thereof; more preferably, neostigmine and salts thereof are exemplified. .

In particular, among components (B), glycyrrhizic acid, neostigmine and their salts are excellent in both the lipid adsorption inhibitory action on nonionic SHCL and the pollen protein accumulation inhibitory action on ionic SHCL. Is preferable.

In the ophthalmic composition for SHCL of the present invention, the blending ratio of the component (B) is appropriately set according to the type of the component (B), the type of the component (A) to be used together, etc. With respect to the total amount of the composition, the total amount of component (B) is 0.0005 to 3.5 w / v%, preferably 0.001 to 2.5%. More specifically, the following ranges are illustrated as a mixture ratio of (B) component.
When component (B) is chlorpheniramine and / or a salt thereof: These are total amounts, usually 0.001 to 0.1 w / v%, preferably 0.006 to 0.03 w / v%, more preferably 0.01 to 0.03 w / v% ;
When component (B) is cromoglycic acid and / or a salt thereof: these are total amounts, usually 0.05 to 3 w / v%
Preferably 0.1 to 2 w / v%, more preferably 0.5 to 1 w / v%;
When component (B) is pranoprofen and / or a salt thereof: These are total amounts, usually 0.001 to 0.2 w / v%, preferably 0.01 to 0.1 w / v%, more preferably 0.01 to 0.05 w / v%. ;
When component (B) is glycyrrhizic acid and / or a salt thereof: These are generally in a total amount of 0.001 to 0.5 w / v%, preferably 0.005 to 0.3 w / v%, more preferably 0.05 to 0.25 w / v%;
When component (B) is neostigmine and / or a salt thereof: These are generally in a total amount of 0.0005 to 0.01 w / v%, preferably 0.0007 to 0.007 w / v%, more preferably 0.001 to 0.005 w / v%.

The blending ratio of the component (B) is preferable from the viewpoint of further enhancing the lipid adsorption inhibiting action on nonionic SHCL and further enhancing the pollen protein accumulation inhibiting action on ionic SHCL.

Further, in the ophthalmic composition for SHCL of the present invention, the ratio of the component (B) to the component (A) is not particularly limited, but further enhances the lipid adsorption inhibitory action on the nonionic SHCL, or From the viewpoint of further enhancing the action of suppressing the adsorption of pollen protein to ionic SHCL, the total amount of the above component (B) is 1 to 100,000 parts by weight, preferably 1 to 50,000 parts by weight per 1 part by weight of the component (A). The range which becomes is illustrated. More specifically, the following range is exemplified as the ratio of the component (B) per 1 part by weight of the total amount of the component (A):
When component (B) is chlorpheniramine and / or a salt thereof: usually 10 to 2000 parts by weight, preferably 20 to 1000 parts by weight, more preferably 30 to 600 parts by weight;
When the component (B) is cromoglycic acid and / or a salt thereof: These are generally in a total amount of 500 to 100,000 parts by weight, preferably 1000 to 50,000 parts by weight, more preferably 1500 to 20,000 parts by weight;
When the component (B) is pranoprofen and / or a salt thereof: these are generally 10 to 5000 parts by weight, preferably 20 to 2000 parts by weight, more preferably 30 to 1000 parts by weight, in total amount;
When the component (B) is glycyrrhizic acid and / or a salt thereof: These are generally 50 to 20000 parts by weight, preferably 100 to 10,000 parts by weight, more preferably 150 to 5000 parts by weight;
When component (B) is neostigmine and / or a salt thereof: These are total amounts, usually 1 to 500 parts by weight, preferably 2 to 200 parts by weight, more preferably 3 to 100 parts by weight.

It is preferable that the ophthalmic composition for SHCL of the present invention further contains a cooling agent. The refreshing agent that can be incorporated into the ophthalmic composition for SHCL of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Specific examples of such a refreshing agent include menthol, anethole, eugenol, camphor, geraniol, cineol, borneol, limonene, and agate. These may be any of d-form, l-form or dl-form, and may be an essential oil containing them. Such essential oils include peppermint oil, cool mint oil, spearmint oil, peppermint oil, fennel oil, cinnamon oil, bergamot oil, eucalyptus oil, rose oil and the like. Among these refreshing agents, menthol, camphor, geraniol, borneol, bergamot oil, and eucalyptus oil are preferable, and menthol, camphor, and geraniol are more preferable from the viewpoint of achieving the effect of the present invention more reliably. , Borneol, and particularly preferably menthol and camphor, and more preferably menthol. These refreshing agents may be used alone or in any combination of two or more.

When a refreshing agent is blended in the ophthalmic composition for SHCL of the present invention, the blending ratio of the refreshing agent varies depending on the type of the refreshing agent used and cannot be uniformly defined. The total amount of the cooling agent is 0.0001 to 1 w / v%, preferably 0.001 to 0.1 w / v%,
More preferably, the ratio is 0.002 to 0.03 w / v%, and particularly preferably 0.005 to 0.02 w / v%.

  The SHCL ophthalmic composition of the present invention preferably further contains an isotonic agent. The isotonic agent that can be incorporated into the ophthalmic composition for SHCL of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Specific examples of such isotonic agents include, for example, disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, sodium hydrogen sulfite, sodium sulfite, potassium chloride, calcium chloride, sodium chloride, magnesium chloride, acetic acid Examples include potassium, sodium acetate, sodium hydrogen carbonate, sodium carbonate, sodium thiosulfate, magnesium sulfate, glycerin, propylene glycol and the like. Among these isotonic agents, glycerin, propylene glycol, sodium chloride, potassium chloride, calcium chloride, and magnesium chloride are preferable from the viewpoint of achieving the effect of the present invention more surely, and more preferably. Sodium chloride or glycerin is mentioned, Especially preferably, sodium chloride is mentioned. These isotonic agents may be used alone or in any combination of two or more.

  When an isotonic agent is blended in the ophthalmic composition for SHCL of the present invention, the blending ratio of the tonicity agent varies depending on the type of tonicity agent used and cannot be defined uniformly. However, for example, the proportion of the tonicity agent is 0.01 to 10 w / v%, preferably 0.05 to 5 w / v%, more preferably 0.1 to 3 w / v% in the total amount. .

The SHCL ophthalmic composition of the present invention preferably further contains a buffer. The buffer that can be incorporated into the ophthalmic composition for SHCL of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Examples of such buffers include borate buffer, phosphate buffer, carbonate buffer, citrate buffer, acetate buffer, epsilon-aminocaproic acid, aspartic acid, aspartate and the like. These buffering agents may be used in combination. Preferred buffering agents are borate buffer, phosphate buffer, carbonate buffer, and citrate buffer, and more preferred are borate buffer and phosphate buffer, and particularly preferred buffer. Is a borate buffer. Examples of the boric acid buffer include boric acid or boric acid salts such as alkali metal borate and alkaline earth metal borate. Examples of the phosphate buffer include phosphoric acid or phosphates such as alkali metal phosphates and alkaline earth metal phosphates. Examples of the carbonate buffer include carbonates or carbonates such as alkali metal carbonates and alkaline earth metal carbonates. Examples of the citrate buffer include citric acid, alkali metal citrate, and alkaline earth metal citrate. Moreover, you may use the borate or the hydrate of a phosphate as a borate buffer or a phosphate buffer. As a more specific example, boric acid or a salt thereof (sodium borate, potassium tetraborate,
Potassium metaborate, ammonium borate, borax, etc.); as phosphate buffer, phosphoric acid or its salt (disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate,
Trisodium phosphate, dipotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate, etc.); as a carbonate buffer, carbonic acid or a salt thereof (sodium bicarbonate, sodium carbonate,
Ammonium carbonate, potassium carbonate, calcium carbonate, potassium bicarbonate, magnesium carbonate, etc.); Citric acid or a salt thereof as a citrate buffer (sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, citric acid) Acetic acid or a salt thereof (ammonium acetate, potassium acetate, calcium acetate, sodium acetate, etc.); aspartic acid or a salt thereof (sodium aspartate, magnesium aspartate, potassium aspartate, etc.), etc. It can be illustrated. Among these buffering agents, boric acid buffering agents are preferably used in the ophthalmic composition for SHCL of the present invention because they are expected to exhibit the effects of the present invention more reliably. These buffering agents may be used alone or in any combination of two or more.

  When a buffering agent is blended with the ophthalmic composition for SHCL of the present invention, the blending ratio of the buffering agent depends on the type of buffering agent used, the type and amount of other blending components, the formulation of the ophthalmic composition, Depending on the total amount of the ophthalmic composition for SHCL, for example, the total amount of the buffer is 0.01 to 10 w / v%, preferably 0.1 to 5 w / Examples are v%, more preferably 0.5 to 2 w / v%.

  The ophthalmic composition for SHCL of the present invention may further contain a surfactant. The surfactant that can be blended in the ophthalmic composition for SHCL of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable, and is a nonionic surfactant. Any of an agent, an amphoteric surfactant, an anionic surfactant, and a cationic surfactant may be used.

Specific examples of the nonionic surfactant that can be incorporated into the ophthalmic composition for SHCL of the present invention include monolauric acid POE (20) sorbitan (polysorbate 20) and monopalmitic acid POE (20) sorbitan (polysorbate 40). POE sorbitan fatty acid esters such as monostearic acid POE (20) sorbitan (polysorbate 60), tristearic acid POE (20) sorbitan (polysorbate 65), monooleic acid POE (20) sorbitan (polysorbate 80); POE / POP block copolymers such as poloxamer 235, poloxamer 188, poloxamer 403, poloxamer 237, poloxamer 124; POE cured castor oil such as POE (60) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 60); POE (9 ) POE alkyl ethers such as lauryl ether; POE-POP alkyl ethers such as POE (20) POP (4) cetyl ether POE (10) POE alkylphenyl ethers such as nonylphenyl ether. In the compounds exemplified above, POE is polyoxyethylene, POP is polyoxypropylene, and the numbers in parentheses indicate the number of moles added. Specific examples of the amphoteric surfactant that can be incorporated into the ophthalmic composition for SHCL of the present invention include alkyldiaminoethylglycine or a salt thereof (for example, hydrochloride). Specific examples of the cationic surfactant that can be incorporated into the ophthalmic composition for SHCL of the present invention include benzalkonium chloride and benzethonium chloride. Specific examples of the anionic surfactant that can be incorporated into the ophthalmic composition for SHCL of the present invention include alkylbenzene sulfonate, alkyl sulfate, polyoxyethylene alkyl sulfate, and aliphatic α-sulfomethyl. Examples include esters and α-olefin sulfonic acids.

  In the ophthalmic composition for SHCL of the present invention, the surfactant may be used alone or in combination of two or more.

Among the above surfactants, preferably nonionic surfactants; more preferably POE sorbitan fatty acid esters, POE hydrogenated castor oil, or POE / POP block copolymers;
More preferably, POE sorbitan fatty acid esters, POE hydrogenated castor oil; particularly preferably polysorbate 80, polyoxyethylene hydrogenated castor oil 60, and poloxamer 407 are used.

When a surfactant is blended in the ophthalmic composition for SHCL of the present invention, the blending ratio of the surfactant is the type of the surfactant, the type and amount of other blended components, the ophthalmic composition for SHCL. It can set suitably according to a formulation form etc. As an example of the blending ratio of the surfactant, the total amount of the surfactant is 0.001 to 1.0 w / v%, preferably 0.005 with respect to the total amount of the ophthalmic composition for SHCL.
-0.7w / v%, More preferably, 0.01-0.5w / v% is illustrated.

  The pH of the ophthalmic composition for SHCL of the present invention is not particularly limited as long as it is within a pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable range. An example of the pH of the ophthalmic composition for SHCL of the present invention is 4.0 to 9.5, preferably 5.0 to 9.0, and more preferably 5.5 to 8.5.

  Further, the osmotic pressure of the ophthalmic composition for SHCL of the present invention is not particularly limited as long as it is within a range acceptable for a living body. As an example of the osmotic pressure ratio of the ophthalmic composition for SHCL of the present invention, a range of preferably 0.5 to 5.0, more preferably 0.6 to 3.0, particularly preferably 0.7 to 2.0. Can be mentioned. The osmotic pressure can be adjusted by a method known in the art using inorganic salts, polyhydric alcohols, sugar alcohols, saccharides and the like. The osmotic pressure ratio is the ratio of the osmotic pressure of the sample to 286 mOsm (0.9 w / v% sodium chloride aqueous solution) based on the 15th revised Japanese pharmacopoeia. Measure with reference to the descent method. The standard solution for measuring the osmotic pressure ratio (0.9 w / v% sodium chloride aqueous solution) was dried in sodium chloride (Japanese Pharmacopoeia standard reagent) at 500 to 650 ° C. for 40 to 50 minutes and then released in a desiccator (silica gel). Cool and accurately measure 0.900 g and dissolve in purified water to make exactly 100 mL, or use a commercially available standard solution for osmotic pressure ratio measurement (0.9 w / v% sodium chloride aqueous solution).

The ophthalmic composition for SHCL of the present invention may contain an appropriate amount of various pharmacologically active components and physiologically active components in addition to the above components, as long as the effects of the present invention are not hindered. Such an ingredient is not particularly limited, and examples thereof include an active ingredient in an ophthalmic drug described in the over-the-counter drug manufacturing (import) approval standard 2000 edition (supervised by the Pharmaceutical Affairs Research Committee). Specifically, the following components are listed as components used in ophthalmic drugs.
Antihistamines: for example, iproheptin, diphenhydramine hydrochloride, ketotifen fumarate, pemirolast potassium and the like.
Decongestant: For example, tetrahydrozoline hydrochloride, naphazoline hydrochloride, naphazoline sulfate, epinephrine hydrochloride, ephedrine hydrochloride, methylephedrine hydrochloride, and the like.
Bactericides: for example, cetylpyridinium, benzalkonium chloride, benzethonium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate and the like.
Vitamins: For example, flavin adenine dinucleotide sodium, cyanocobalamin, retinol acetate, retinol palmitate, pyridoxine hydrochloride, panthenol, calcium pantothenate and the like.
Amino acids: For example, potassium aspartate, magnesium aspartate, aminoethylsulfonic acid and the like.
Anti-inflammatory agent: for example, allantoin, azulene, sodium azulenesulfonate, guaiazulene, ε-aminocaproic acid, berberine chloride, berberine sulfate, lysozyme chloride, and the like.
Astringent: For example, zinc white, zinc lactate, zinc sulfate and the like.
Other: For example, chondroitin sulfate sodium, sulfamethoxazole, sulfamethoxazole sodium and the like.

In addition, in the ophthalmic composition for SHCL of the present invention, various additives are appropriately selected according to a conventional method according to its use and form as long as they do not impair the effects of the invention, and one or more of them are selected. May be used in an appropriate amount. Examples of these additives include various additives described in Pharmaceutical Additives Encyclopedia 2007 (edited by Japan Pharmaceutical Additives Association). Typical additives include the following additives.
Carrier: An aqueous carrier such as water or hydrous ethanol.
Thickeners: for example, carboxyvinyl polymer, hydroxyethylcellulose, hydroxypropylmethylcellulose, methylcellulose, alginic acid, polyvinyl alcohol (completely or partially saponified product), polyvinylpyrrolidone, macrogol and the like.
Sugars: For example, cyclodextrins and the like.
Sugar alcohols: For example, xylitol, sorbitol, mannitol and the like. These may be d-form, l-form or dl-form.
Preservatives, bactericides or antibacterial agents: for example, alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, paraoxy Methyl benzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, Glow Kill (trade name, manufactured by Rhodia) and the like.
pH adjuster: for example, hydrochloric acid, boric acid, aminoethylsulfonic acid, epsilon-aminocaproic acid, citric acid, acetic acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sodium bicarbonate, sodium carbonate, boro Sand, triethanolamine, monoethanolamine, diisopropanolamine, sulfuric acid, phosphoric acid, polyphosphoric acid, propionic acid, oxalic acid, gluconic acid, fumaric acid, lactic acid, tartaric acid, malic acid, succinic acid, gluconolactone, ammonium acetate etc.
Stabilizers: for example, dibutylhydroxytoluene, trometamol, sodium formaldehyde sulfoxylate (Longalite), tocopherol, sodium pyrosulfite, monoethanolamine, aluminum monostearate, glyceryl monostearate and the like.
Chelating agents: for example, ethylenediaminediacetic acid (EDDA), ethylenediaminetriacetic acid, ethylenediaminetetraacetic acid (edetic acid, EDTA), N- (2-hydroxyethyl) ethylenediaminetriacetic acid (HEDTA), diethylenetriaminepentaacetic acid (DTPA), and the like.

  The ophthalmic composition for SHCL of the present invention is prepared by adding a desired amount of the above-mentioned components (A) and (B) and, if necessary, other blending components to a desired concentration.

  The ophthalmic composition for SHCL of the present invention is not particularly limited as long as it can be used in the ophthalmic field, and examples thereof include liquids and ointments. Among these, liquid is preferable. Of the liquids, aqueous liquids are preferred. When the ophthalmic composition for SHCL of the present invention is made into an aqueous liquid, pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable water may be used as an aqueous carrier. Specifically, distilled water, normal water, purified water, sterilized purified water, water for injection, distilled water for injection and the like are exemplified. These definitions are based on the 15th revision Japanese Pharmacopoeia. Here, the aqueous liquid means a liquid form containing water, and usually 1% by weight or more, preferably 5% by weight or more, more preferably 20% by weight or more of water in the ophthalmic composition for SHCL. More preferably, it means one containing 50% by weight or more.

  The ophthalmic composition for SHCL of the present invention is not limited in its formulation form as long as it is used in the ophthalmic field and is used so as to come into contact with SHCL. For example, eye drops for SHCL (eye drops that can be used while wearing SHCL), eye drops for SHCL (eye wash that can be used while wearing SHCL), SHCL wearing liquid, SHCL care liquid (SHCL disinfectant, SHCL Storage solution, SHCL cleaning solution, SHCL cleaning storage solution, etc.).

  Among these, eye drops for SHCL are preparations that are frequently used per day, and can effectively suppress lipid adsorption to SHCL. In view of the lipid adsorption inhibiting action, an example of a suitable formulation form of the ophthalmic composition for SHCL is an eye drop for SHCL.

Moreover, the eye drops for SHCL, the eye wash for SHCL, the detergent for SHCL, especially the eye drops for SHCL are preparation forms that strongly require the action of suppressing the accumulation of pollen proteins in ionic SHCL. In view of this viewpoint, as a suitable example of the ophthalmic composition for SHCL of the present invention, an eye drop for SHCL, an eye wash for SHCL,
And SHCL cleaning agents, particularly preferably SHCL eye drops.

  The method for using the ophthalmic composition for SHCL of the present invention is not particularly limited as long as it is a known method having a step of bringing the ophthalmic composition for SHCL into contact with SHCL. For example, in the case of SHCL eye drops, an appropriate amount of the eye drops may be instilled before or during the wearing of the SHCL, and it is particularly preferable to instill with the SHCL attached. In the case of an SHCL eye wash, an appropriate amount of the eye wash may be used for eye washing before or during the wearing of the SHCL, and it is particularly preferable to wash the eye with the SHCL attached. In addition, when the ophthalmic composition for SHCL of the present invention is an eye drop for SHCL or an eye wash for SHCL, it can be used for the purpose of eye drops or eye wash even when not wearing SHCL. it can. Moreover, in the case of SHCL mounting liquid, it is used by contacting SHCL with an appropriate amount of the mounting liquid when SHCL is mounted. Furthermore, in the case of an SHCL care solution, it is used by immersing SHCL in an appropriate amount of the care solution, or by bringing SHCL into contact with the care solution and scrubbing.

In the ophthalmic composition for SHCL of the present invention, the type of SHCL to be applied is not particularly limited, and any SHCL that is currently marketed or will be marketed in the future regardless of whether it is ionic or nonionic. Can be applied. According to the ophthalmic composition for SHCL of the present invention, when nonionic SHCL is an application target, adsorption of lipids to nonionic SHCL can be suppressed. In addition, when ionic SHCL is an application target, accumulation of pollen protein in ionic SHCL can be suppressed. Here, ionic refers to the content of ionic components in contact lens materials of 1 mol% or more in accordance with US FDA (US Food and Drug Administration) standards, and nonionic refers to US FDA ( According to US Food and Drug Administration standards, the content of ionic components in contact lens materials is less than 1 mol%.

In the ophthalmic composition for SHCL of the present invention, the moisture content of the SHCL to be applied is not particularly limited, and examples thereof include 90% or less, preferably 60% or less, and more preferably 50% or less. Since SHCL contains a hydrogel material, it contains at least more than 0% moisture.

  Here, the moisture content of SHCL indicates the ratio of water in SHCL, and is specifically determined by the following calculation formula.

Moisture content (%) = (weight of hydrated water / weight of hydrated SHCL) x 100
Such moisture content can be measured by a gravimetric method according to the description of ISO18369-4: 2006.

  In addition, compared to non-silicone hydrogel contact lenses, which are generally soft, SHCL, which is a hard material, tends to cause deterioration of the feeling of use due to lens deformation and reduced wettability due to the adsorption of foreign substances, and tends to cause ocular mucosal damage. It is in. According to the ophthalmic composition for SHCL of the present invention, it is possible to effectively suppress the accumulation of lipids and pollen proteins in the hard material SHCL that easily causes deterioration of the feeling of use and ocular mucosal damage, and thereby the lens. By preventing deformation and alteration, it is possible to effectively prevent deterioration of the feeling of use and ocular mucosal damage. In view of the effects of the present invention, SHCL having a relatively high hardness can be cited as a suitable application target of the ophthalmic composition for SHCL of the present invention. Preferably, the hardness of SHCL to be applied is 3 g or more, preferably 4 g or more, more preferably 6 g or more, and still more preferably 8 g or more when measured by the following measuring method using a texture analyzer. Further, the upper limit value of the hardness of the SHCL to be applied is not particularly limited, but is preferably 15 g or less, more preferably 12 g or less.

Contact lens hardness is measured with a texture analyzer (Product name: TA.XT.plus TEXTURE
Using ANALYSER (manufactured by Stable Micro Systems Limited)), it can be measured specifically as follows.

First, remove the contact lens to be measured from the package, wipe off excess water, rinse with physiological saline (0.9% sodium chloride aqueous solution), and then raise the convex surface on the bottom of the plastic petri dish filled with physiological saline. Arrange so that Next, the contact lens is adjusted to be directly below the probe of the measuring instrument, and measurement is performed under the following measurement conditions.

[Measurement condition]
Instrument settings:
Test mode Compression measurement Probe type φ10mm cylinder probe
Target Mode Distance
Distance 2.5mm
Triger Type Auto
Triger Force 0.1g
Test Speed 1.0mm / sec
Measure the stress when crushing the lens 2.5mm (2.5 seconds) after the probe starts to push down the lens apex, and record the maximum value as hardness.

The ophthalmic composition for SHCL of the present invention can exhibit intrinsic physiological activity based on the above components (A) and (B) and can be used for various applications. For example, based on the component (A), it may be used for antiseptic, sterilization, and disinfection, and based on the component (B), it is used for applications such as anti-allergy, anti-inflammation, and improvement of eye focus adjustment function. You can also.

  In addition, the ophthalmic composition for SHCL of the present invention can effectively prevent corneal epithelial disorders such as corneal staining caused by lipid adsorption to nonionic SHCL. Can also be used.

  Furthermore, since the ophthalmic composition for SHCL of the present invention promotes the removal of pollen protein from ionic SHCL and can prevent reattachment, the accumulation of pollen protein in ionic SHCL can be effectively suppressed. Therefore, the pollen protein adsorbed on the contact lens is prevented from being kept in contact with the eye for a long time, and it is also effective in preventing allergy and preventing deterioration due to pollen. Therefore, it is suitable for application to ionic SHCL users of hay fever or hay fever reserve.

2. Method for inhibiting lipid adsorption to nonionic SHCL, and method for imparting action to inhibit lipid adsorption to nonionic SHCL As described above, by using the components (A) and (B) together, nonionic It is possible to suppress the adsorption of lipids to sex SHCL.

Therefore, the present invention, from another viewpoint, (A) at least one selected from the group consisting of polyhexanide and a salt thereof, and (B) chlorpheniramine, cromoglycic acid, pranoprofen, glycyrrhizic acid, neostigmine And an ophthalmic composition for SHCL containing at least one selected from the group consisting of these salts and non-ionic SHCL, which inhibits lipid adsorption to non-ionic SHCL Provide a way to do it. Furthermore, in the ophthalmic composition for SHCL, (A) at least one selected from the group consisting of polyhexanide and salts thereof, (B) chlorpheniramine, cromoglycic acid, pranoprofen, glycyrrhizic acid, neostigmine and these And a method for imparting an action of suppressing the adsorption of lipids to nonionic SHCL to an ophthalmic composition for SHCL, comprising blending at least one selected from the group consisting of salts of

  In these methods, the types and mixing ratios of the components (A) and (B), the types and mixing ratios of the other components to be mixed, the dosage form of the ophthalmic composition for SHCL, and the types of nonionic SHCL to be applied The same as in “1. SHCL ophthalmic composition”.

3. A method for suppressing the accumulation of pollen protein in ionic SHCL, and a method for imparting an inhibitory action on the accumulation of pollen protein in ionic SHCL. Also, as described above, the above components (A) and (B) are used in combination. Can promote pollen protein removal from ionic SHCL and prevent reattachment even when ionic SHCL wearing eyes are exposed to pollen, thus suppressing pollen protein accumulation in ionic SHCL become. Therefore, the present invention, from another viewpoint, (A) at least one selected from the group consisting of polyhexanide and a salt thereof, and (B) chlorpheniramine, cromoglycic acid, pranoprofen, glycyrrhizic acid, neostigmine And an ophthalmic composition for SHCL containing at least one selected from the group consisting of these salts, and the ionic SHCL, the method for suppressing adsorption of pollen protein to the ionic SHCL I will provide a. Furthermore, in the ophthalmic composition for SHCL, (A) at least one selected from the group consisting of polyhexanide and a salt thereof, and (B) chlorpheniramine, cromoglycic acid, pranoprofen, glycyrrhizic acid, neostigmine and these And a method of imparting to the ophthalmic composition an action of suppressing the accumulation of pollen protein in ionic SHCL, which comprises blending at least one selected from the group consisting of salts of

  In these methods, the types and blending ratios of components (A) and (B), the types and blending ratios of other components to be blended, the formulation form of the ophthalmic composition for SHCL, the types of ionic SHCL to be applied, etc. Is the same as “1. Ophthalmic composition for SHCL”.

  EXAMPLES The present invention will be described in detail below based on examples, but the present invention is not limited to these examples.

Reference Test Example 1: Evaluation of lipid adsorbability of various SCLs The following experiments were conducted using the various soft contact lenses shown in Table 1, and the lipid adsorbability of the soft contact lenses was evaluated. The soft contact lenses used in this test are all commercially available products.

First, fluorescently labeled lipid (N- (fluorescein-5-thiocarbamoyl) -1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine, triethylammonium salt; manufactured by invitrogen) 1 mg / ml
Prepared as a fluorescent lipid solution by adding physiological saline (0.9w / v% sodium chloride) to 500μL of a mixed solution of chloroform and methanol at a concentration ratio of 1: 4 in a volume ratio of 1: 4 to make a total volume of 20ml did. Each soft contact lens was immersed in physiological saline for overnight or longer and pre-tested. As a sample group, each soft contact lens was immersed in 1 ml of a fluorescent lipid solution in a 24-well microplate and shaken at 34 ° C. for 24 hours. Moreover, each soft contact lens was immersed one by one in physiological saline as a blank group, and the same shaking treatment as the sample group was performed. After 24 hours, each soft contact lens was transferred to a plate containing 1 ml of fresh physiological saline, and the fluorescence intensity of each well was measured using a fluorescence plate reader (Thermo Fisher Scientific Inc.) (excitation wavelength: 485 nm, (Fluorescence wavelength: 538 nm). A value obtained by subtracting the fluorescence intensity of the blank group from the fluorescence intensity of the sample group was calculated as an index of the amount of adsorbed lipid.

  The results are shown in FIG. As is clear from FIG. 1, the lipid adsorption amount of nonionic SHCL (lenses A and B) is significantly larger than that of ionic SHCL (lens C) and conventional hydrogel lenses (lenses D to F). It was confirmed that the problem of lipid contamination was serious.

Test Example 1: Evaluation of SHCL Lipid Adsorption Inhibition Each test solution shown in Tables 2 to 7 below (Example 1-1) using nonionic SHCL (Lens A) in which significant lipid adsorption was observed in Reference Test Example 1 above. The effect of nonionic SHCL on lipid adsorption was examined using ˜1-16 and Comparative Examples 1-1 to 1-18).

First, 1 mg / ml of fluorescently labeled lipid (N- (fluorescein-5-thiocarbamoyl) -1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine, triethylammonium salt; manufactured by invitrogen)
A physiological lipid (0.9 w / v% sodium chloride) was added to 500 μL of a mixed solution in which a chloroform solution and methanol were mixed at a volume ratio of 1: 4, and a total volume of 20 ml was prepared as a fluorescent lipid solution. Lens A was immersed in physiological saline for one night or longer and pre-test treatment was performed. Next, 200 μL of each test solution (Examples 1-1 to 1-11 and Comparative Example 1-1) was added to each well of a 24-well microplate.
~ 1-12) and wells containing 1000 μL of fluorescent lipid solution were prepared, and the lens A that had undergone the pre-test treatment was immersed one by one in the well and subjected to shaking treatment at 34 ° C. for 24 hours (sample) group). In addition, 200 μL of each test solution (Examples 1-1 to 1-11 and Comparative Examples 1-1 to 1-12) and 1000 μL of physiological saline were prepared as a blank group, and before that, The lens A that had been processed was immersed one by one and similarly shaken (blank group). After 24 hours, each lens A after the shaking treatment was transferred to a plate containing 1 ml of new physiological saline, and the fluorescence intensity of each well was measured using a fluorescence plate reader (Thermo Fisher Scientific Inc.) ( Excitation wavelength: 485 nm, fluorescence wavelength: 538 nm). The value obtained by subtracting the fluorescence intensity of the blank group from the fluorescence intensity of each sample group is obtained as an index of the amount of adsorbed lipid, and the amount of adsorbed lipid of the test solution (control test solution) consisting of sodium chloride, borate buffer and purified water is calculated as 100 The relative value (%) of the amount of adsorbed lipid in each test solution was calculated. Specifically, for the test solutions of Examples 1-1 to 1-5 and Comparative Examples 1-2 to 1-6, Comparative Example 1-1 is a control test solution, Examples 1-6 to 1-11 and a comparison For the test solutions of Examples 1-8 to 1-12, using Comparative Example 1-7 as a control test solution, the relative value (%) of the amount of adsorbed lipid of each test solution was determined.

  In addition, when Examples 1-12 to 1-16 and Comparative Examples 1-13 to 1-18 were used as test solutions, wells containing 600 μL of each test solution and 600 μL of a fluorescent lipid solution were prepared as a sample group. Wells containing 600 μL of each test solution and 600 μL of physiological saline as a blank group were prepared and tested in the same manner as described above. The relative value (%) of the amount of adsorbed lipid in each test solution is the control solution of Comparative Example 1-13 for the test solutions of Examples 1-12 to 1-16 and Comparative Examples 1-14 to 1-18. It calculated | required similarly to the above.

The obtained results are shown in FIGS. As shown in FIGS. 2-4, when using PHMB, chlorpheniramine maleate, sodium cromoglycate, pranoprofen, dipotassium glycyrrhizinate, or neostigmine methylsulfate alone, effective lipid adsorption inhibitory effect is I was not able to admit. On the other hand, unexpectedly, when PHMB is used in combination with chlorpheniramine maleate, sodium cromoglycate, pranoprofen, dipotassium glycyrrhizinate, or neostigmine methylsulfate (Examples 1-1 to 1) -16)
It was shown that lipid adsorption on nonionic SHCL can be suppressed synergistically.

Moreover, as a result of preparing the test solutions of Examples 1-1 to 1-16 as eye drops and instilling them while wearing nonionic SHCL, the feeling of use of nonionic SHCL was kept good.

Reference Test Example 2: Evaluation of Pollen Protein Adsorption Characteristics to Soft Contact Lenses Four kinds of soft contact lenses shown in Table 8 were used in the test to evaluate the pollen protein adsorption characteristics to the soft contact lenses.

First, the lenses used for the test were immersed one by one in 4 mL of physiological saline and stored overnight at room temperature (lens pretreatment).

Pollen protein antigen ( CEL Pollen Extract-Ja, manufactured by LSL Co., Ltd.) Properties: Lyophilized powder (Cedar Pollen crude extract Mountain ceder , extracted from Juniperus Asheii pollen)
) Was dissolved in physiological saline to prepare a 5 mg / 30 mL pollen protein solution. In each hole of the 24-well plate, 1.0 mL of pollen protein solution was put, and after wiping off excess moisture from the pretreated lens, it was immersed and shaken at 34 ° C. and 120 rpm for 18 hours. Next, take out the lens, quickly soak (about 1 second) in 100 mL of physiological saline, rinse the excess liquid, and then lightly drain the water using the edge of a beaker, then put the pollen protein into each hole of the 24-well plate. It was immersed in 1 mL of separation liquid (aqueous solution containing 1% sodium carbonate and 1% SDS). The mixture was shaken at 34 ° C. and 120 rpm for 3 hours to separate the pollen protein adsorbed on the lens into the pollen protein separation solution.

Using a micro BCA assay kit (Thermo SCIENTIFIC, Pierce # 23235), the amount of pollen protein in the pollen protein separation solution was quantified as an albumin equivalent value to determine the amount of pollen protein adsorbed to the lens.

The hardness of each soft contact lens is a value measured using a texture analyzer (product name: TA.XT.plus TEXTURE ANALYSER (manufactured by Stable Micro Systems Limited)) as described above.

  The results are shown in FIG. As shown in FIG. 5, when the lens 1 that is ionic SHCL is used, the lens 3 and the lens 4 that are non-silicon soft contact lenses and the lens 2 that is non-ionic SHCL are remarkably different. High pollen protein adsorption was observed. From this result, pollen protein tends to adsorb very large amount to ionic SHCL among soft contact lenses, and ionic SHCL has a unique problem that it is very easy to adsorb pollen protein. Was confirmed.

Test Example 2: Evaluation of Pollen Protein Accumulation Suppression against Ionic SHCL The following test was carried out using the lens 1 (ionic SHCL) in which significant adsorption of pollen protein was confirmed in Reference Test Example 2 above.

First, the lenses 1 were immersed one by one in 5 mL of physiological saline and stored at room temperature for 5 hours (lens pretreatment). Pollen protein antigen (CEL Pollen Extract-Ja, manufactured by LSL Co., Ltd.) Properties: Lyophilized powder (Cedar Pollen crude extract Mountain ceder, extracted from pollen of Juniperus Asheii) in physiological saline, A 5 mg / 50 mL pollen protein solution was prepared. 1.0 mL of the pollen protein solution was put into each hole of the 24-well plate, the excess moisture of the pretreated lens was wiped off and immersed, and shaken at 34 ° C. and 400 rpm for 24 hours.

The lens 1 immersed in the pollen protein solution is taken out, quickly immersed in 100 mL of physiological saline (about 1 second), rinsed with excess liquid, wiped off moisture, and placed in a 24-well plate. Each test solution (Examples 2-1 to 2-2 and Comparative Examples 2-1 to 2-4) was immersed in 1.0 mL and shaken at 34 ° C. and 400 rpm for 18 hours. After that, take out the lens 1, soak it quickly (about 1 second) in 100 mL of physiological saline, rinse the excess liquid, and then use a beaker's edge to lightly drain the water and place it in a 24-well plate. It was immersed in 0.5 mL of the liquid for use (aqueous solution containing 1% sodium carbonate and 1% SDS). The mixture was shaken at 34 ° C. and 400 rpm for 3 hours to separate the pollen protein adsorbed on the lens into the pollen protein separation solution.

  Moreover, in order to calculate the amount of pollen protein adsorption more accurately by subtracting the influence of each test solution, as a blank group, except that the step of treating with the pollen protein solution was changed to treatment with physiological saline, In the same manner as described above, a sample treated with each test solution and treated with a pollen protein separating solution was prepared.

Using a micro BCA assay kit (Thermo SCIENTIFIC, Pierce # 23235), the amount of pollen protein present in the pollen protein separation solution was quantified as an albumin equivalent, and the amount of pollen protein detached from lens 1 (pollen) Protein adsorption amount) was determined. In calculating the amount of pollen protein adsorbed, the amount of pollen protein adsorbed was determined by subtracting the absorbance of the blank group from the absorbance of each sample and calculating it as an albumin equivalent value. Next, according to the following formula, from the ratio of the amount of pollen protein adsorbed when using the test solution of each comparative example and example to the amount of pollen protein adsorbed when using the test solution of Comparative Example 2-4, pollen protein adsorption The improvement rate (%) was calculated.

  The results are shown in FIG. From these results, PHMB, dipotassium glycyrrhizinate or neostigmine methylsulfate did not improve pollen protein accumulation when used alone (Comparative Examples 2-1 to 2-3). On the other hand, unexpectedly, when PHMB is used in combination with dipotassium glycyrrhizinate or neostigmine methylsulfate (Examples 2-1 and 2-2), the pollen protein adsorption improvement rate is synergistic. It was clarified that the amount of pollen protein adsorbed to ionic SHCL can be effectively reduced and accumulation can be suppressed.

Formulation Example According to the formulation shown in Table 10, eye drops for SHCL (Example 3-7), SHCL wearing solution (Example 8), SHCL wearing and eye drops (Example 9), SHCL eyewash (Example 10) ), And an SHCL cleaning solution (Examples 11-12).

Claims (1)

A silicone hydrogel contact lens comprising (A) polyhexanide hydrochloride and (B) at least one selected from the group consisting of chlorpheniramine, cromoglycic acid, pranoprofen, glycyrrhizic acid, neostigmine and salts thereof. Ophthalmic composition.

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